Decorin prevents the development of juvenile communicating hydrocephalus

Hannah Botfield, Ana Maria Gonzalez, Osama Abdullah, Anders Dæhli Skjolding, Martin Berry, James Pat Mcallister, Ann Logan

Research output: Contribution to journalArticle

Abstract

In post-haemorrhagic and other forms of communicating hydrocephalus, cerebrospinal fluid flow and drainage is obstructed by subarachnoid fibrosis in which the potent fibrogenic cytokine transforming growth factor-β has been aetiologically implicated. Here, the hypothesis that the transforming growth factor-β antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-β1 and phosphorylated Smad2/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-β-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.

Original languageEnglish (US)
Pages (from-to)2842-2858
Number of pages17
JournalBrain
Volume136
Issue number9
DOIs
StatePublished - Jan 1 2013

Fingerprint

Decorin
Hydrocephalus
Transforming Growth Factors
Kaolin
Fibrosis
Brain
Intraventricular Infusions
Subarachnoid Space
Injections
Laminin
Fibronectins
Neuroglia
Extracellular Matrix
Histology
Therapeutics
Immunohistochemistry
Phosphates
Magnetic Resonance Imaging
Pathology
Cytokines

Keywords

  • decorin
  • fibrosis
  • hydrocephalus
  • Smad
  • TGF-β

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Botfield, H., Gonzalez, A. M., Abdullah, O., Skjolding, A. D., Berry, M., Mcallister, J. P., & Logan, A. (2013). Decorin prevents the development of juvenile communicating hydrocephalus. Brain, 136(9), 2842-2858. https://doi.org/10.1093/brain/awt203

Decorin prevents the development of juvenile communicating hydrocephalus. / Botfield, Hannah; Gonzalez, Ana Maria; Abdullah, Osama; Skjolding, Anders Dæhli; Berry, Martin; Mcallister, James Pat; Logan, Ann.

In: Brain, Vol. 136, No. 9, 01.01.2013, p. 2842-2858.

Research output: Contribution to journalArticle

Botfield, H, Gonzalez, AM, Abdullah, O, Skjolding, AD, Berry, M, Mcallister, JP & Logan, A 2013, 'Decorin prevents the development of juvenile communicating hydrocephalus', Brain, vol. 136, no. 9, pp. 2842-2858. https://doi.org/10.1093/brain/awt203
Botfield H, Gonzalez AM, Abdullah O, Skjolding AD, Berry M, Mcallister JP et al. Decorin prevents the development of juvenile communicating hydrocephalus. Brain. 2013 Jan 1;136(9):2842-2858. https://doi.org/10.1093/brain/awt203
Botfield, Hannah ; Gonzalez, Ana Maria ; Abdullah, Osama ; Skjolding, Anders Dæhli ; Berry, Martin ; Mcallister, James Pat ; Logan, Ann. / Decorin prevents the development of juvenile communicating hydrocephalus. In: Brain. 2013 ; Vol. 136, No. 9. pp. 2842-2858.
@article{3b9f384d180e45099c5700a97d1e30b3,
title = "Decorin prevents the development of juvenile communicating hydrocephalus",
abstract = "In post-haemorrhagic and other forms of communicating hydrocephalus, cerebrospinal fluid flow and drainage is obstructed by subarachnoid fibrosis in which the potent fibrogenic cytokine transforming growth factor-β has been aetiologically implicated. Here, the hypothesis that the transforming growth factor-β antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-β1 and phosphorylated Smad2/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-β-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.",
keywords = "decorin, fibrosis, hydrocephalus, Smad, TGF-β",
author = "Hannah Botfield and Gonzalez, {Ana Maria} and Osama Abdullah and Skjolding, {Anders D{\ae}hli} and Martin Berry and Mcallister, {James Pat} and Ann Logan",
year = "2013",
month = "1",
day = "1",
doi = "10.1093/brain/awt203",
language = "English (US)",
volume = "136",
pages = "2842--2858",
journal = "Brain",
issn = "0006-8950",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Decorin prevents the development of juvenile communicating hydrocephalus

AU - Botfield, Hannah

AU - Gonzalez, Ana Maria

AU - Abdullah, Osama

AU - Skjolding, Anders Dæhli

AU - Berry, Martin

AU - Mcallister, James Pat

AU - Logan, Ann

PY - 2013/1/1

Y1 - 2013/1/1

N2 - In post-haemorrhagic and other forms of communicating hydrocephalus, cerebrospinal fluid flow and drainage is obstructed by subarachnoid fibrosis in which the potent fibrogenic cytokine transforming growth factor-β has been aetiologically implicated. Here, the hypothesis that the transforming growth factor-β antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-β1 and phosphorylated Smad2/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-β-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.

AB - In post-haemorrhagic and other forms of communicating hydrocephalus, cerebrospinal fluid flow and drainage is obstructed by subarachnoid fibrosis in which the potent fibrogenic cytokine transforming growth factor-β has been aetiologically implicated. Here, the hypothesis that the transforming growth factor-β antagonist decorin has therapeutic potential for reducing fibrosis and ventriculomegaly was tested using a rat model of juvenile communicating hydrocephalus. Hydrocephalus was induced by a single basal cistern injection of kaolin in 3-week-old rats, immediately followed by 3 or 14 days of continuous intraventricular infusion of either human recombinant decorin or phosphate-buffered saline (vehicle). Ventricular expansion was measured by magnetic resonance imaging at Day 14. Fibrosis, transforming growth factor-β/Smad2/3 activation and hydrocephalic brain pathology were evaluated at Day 14 and the inflammatory response at Days 3 and 14 by immunohistochemistry and basic histology. Analysis of ventricular size demonstrated the development of hydrocephalus in kaolin-injected rats but also revealed that continuous decorin infusion prevented ventricular enlargement, such that ventricle size remained similar to that in intact control rats. Decorin prevented the increase in transforming growth factor-β1 and phosphorylated Smad2/3 levels throughout the ventricular system after kaolin injection and also inhibited the deposition of the extracellular matrix molecules, laminin and fibronectin in the subarachnoid space. In addition, decorin protected against hydrocephalic brain damage inferred from attenuation of glial and inflammatory reactions. Thus, we conclude that decorin prevented the development of hydrocephalus in juvenile rats by blocking transforming growth factor-β-induced subarachnoid fibrosis and protected against hydrocephalic brain damage. The results suggest that decorin is a potential clinical therapeutic for the treatment of juvenile post-haemorrhagic communicating hydrocephalus.

KW - decorin

KW - fibrosis

KW - hydrocephalus

KW - Smad

KW - TGF-β

UR - http://www.scopus.com/inward/record.url?scp=84883396629&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883396629&partnerID=8YFLogxK

U2 - 10.1093/brain/awt203

DO - 10.1093/brain/awt203

M3 - Article

C2 - 23983032

AN - SCOPUS:84883396629

VL - 136

SP - 2842

EP - 2858

JO - Brain

JF - Brain

SN - 0006-8950

IS - 9

ER -